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Psychotherapeutic
or Psychotropic
Medications
Antidepressants
Many varieties
Antianxiety drugs
Antidepressants
Mood Stabilizers
Major Depression is the 3rd most disabling disease worldwide.
It currently affects 30 million Americans (only about 21% get
treatment) & accounts for ~70% of psychiatric hospitalizations
and ~40% of suicides. 10% of males and 25% of females will
suffer clinical depression in their lifetimes.
Antipsychotics
(all these category names should be viewed as
indicating just 1 of the prominent uses of the drugs)
Over 230 million prescriptions/yr in US
At least 10-15% of the population receiving psychotherapeutics
Symptoms of Major Depressive Disorder
• At least 5 of the following almost every day
weeks:
• Persistent depressed or irritable mood
• Decreased interest or pleasure
• Significant change in appetite/weight
• Insomnia or hypersomnia
• May move & talk slowly, or may be restless
• Fatigue, loss of energy or motivation, apathetic
• Feel worthless; inappropriate guilt
• Can’t make decisions, concentrate
• Suicidal thoughts or actions
for at least 2
• This family of
transmitters is
known as the
monoamines.
• Symptoms of psychosis in severe cases
Original Monoamine Theory of Mood
• Normal mood depends on appropriate levels of
monoamine activity in brain.
• Levels too low  depression
• Levels too high euphoria, mania
• All current antidepressants have actions which would help
normalize these deficiencies.
Monoamine Theory Updated
Based on New Research
• Antidep drugs all increase monoamine activity immediately, but aren’t
clinically effective for weeks. It appears that slower, long term effects
of these drugs are key to the clinical improvement.
• Formation of new neurons (neurogenesis) & repair of damaged
neurons are normal processes in certain brain areas (hippocampus,
frontal cortex)
• Psychological stress as well as many physiological stresses decrease
neurogenesis and neuron repair.
• All with depression probably don’t experience exactly the
same monoamine imbalance.
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Neurogenic Theory of Depression
• Depression (stress-related & stressful itself) is associated
with loss of neurons & decreased neurogenesis. It is a
neurodegenerative disease like Alzheimer’s or Parkinson’s,
but affecting different regions.
• The increased monoamine activity caused by antideps
stimulates intracellular production of substances which
promote neuron repair and neurogenesis necessary to
replace the neurons lost in depression. Growth of new
neurons takes time.
Tricyclics
Categories of Antidepressants
• First Generation Antidepressants (‘50’s-’60’s):
• Tricyclic antidepressants (TCAs)
• Monoamine oxidase inhibitors (MAOIs)
• Second Generation Antidepressants (‘89 )
• Selective serotonin reuptake inhibitors (SSRIs)
• Dual action antidepressants (2000)
• Miscellaneous group
Tricyclic Antidepressants
(TCAs)
• Best known:
•
•
•
•
*imipramine (Tofranil)
Classic examples of this group
*amitriptyline (Elavil)
*desipramine (Norpramin)
Newer & fewer side effects, so
*nortriptyline (Pamelor, Aventil)
preferred among the TCAs today
• Significantly more effective than placebo in providing relief
for severe depression & sustained prevention of depressive
episodes. Not as effective for psychotic or atypical forms of
depression.
• Usually taken once a day at bedtime
• Very inexpensive
Tricyclics Block Reuptake of 5HT & NE so transmitter activates
receptors longer
• Even though these are old drugs they have a useful combination of
effects:
• Antidepressant
• Anti-anxiety
• Analgesic
• Sedating
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Tricyclic Problems
• Delayed effectiveness (3-6 weeks); therapeutic window for
effectiveness
• Also block ACh & histamine receptors- may cause annoying
side effects before benefits are felt:
• Anticholinergic: Dry mouth, dizzy, blurred vision, constipation,
urinary hesitance, tachycardia, *possible cognitive problems (not
recommended for young or old)
• Antihistamine: sedation
• Have a low safety margin & are lethal in overdose (cardiac
arrhythmia & heart failure, coma, respiratory
distress10,000 ER, 800 deaths); interact with a wide
variety of drugs. Had been #1 cause of prescription drug
overdose death in US in past (before opioids)
Table 12.1
Claire D. Advokat, Joseph E. Comaty, Robert M. Julien: Julien’s Primer of Drug Action, Thirteenth Edition
Copyright © 2014 by Worth Publishers
Monoamine Oxidase Inhibitors
(MAOIs)
Other Uses for Tricyclics
• dysthymia (milder but persistent depression) or the
depression of bipolar disorder
• OCD (clomipramine is a favorite)
• panic disorder/agoraphobia & other anxiety disorders
• treatment of chronic pain conditions, migraine, chronic
fatigue
• treatment of enuresis (bed-wetting)
• some cases of ADHD*
• * Caution necessary: have been 12 deaths in kids using TCAs
MAOI Problems
• Foods with high levels of tyramine must be avoided
• Drugs with sympathomimetic or NE/5HT effects must be avoided,
including other antidepressants
• Neglecting restrictions can result in life-threatening hypertensive crisis
(severe headache, skyrocketing blood pressure, heart palpitations);
must continue restrictions 2 weeks after stopping drug as well
• Clinical improvement delayed
• selegiline (Ensam) patch – slow transdermal absorption seems to
avoid food/drug interactions while still being effective. While
expensive this may result in more frequent prescribing for the
conditions for which MAOIs are particularly effective (e.g. atypical
depressions, depression in elderly, anorexia, bulimia) or in those
patients who do not respond to other antidepressants.
• *phenelzine (Nardil), tranylcypromine (Parnate),
isocarboxazid (Marplan, Enerzer)
• Inhibit action of MAO, an enzyme which breaks down 5HT,
DA and NE, allowing more transmitter release/action
• Problem : enzyme is inhibited not only in brain but also in
body where it serves an important protective function
Low Tyramine Diet
•
Foods to Avoid
• Medications to Avoid
•
Aged cheeses (including cheddar, American, mozzarella
as on pizza; cream cheese, farmer cheese, cottage cheese
are considered safe)
• (ask your physician about any other prescribed
medications for safety)
•
Yeast extract (may be a component of certain canned
soups; baked products raised with yeast are acceptable)
•
Red wine (especially Chianti; white wine in moderation
will not cause a hypertensive reaction)
•
Beer or ale (tyramine content varies from lot to lot)
•
Pickled herring, canned sardines, anchovies, caviar
•
Any meat or fish which is not fresh, freshly canned, or
freshly frozen (including lox, salami, sausage, corned beef,
liver pate)
•
•
Broad beans or fava beans
Canned figs, stewed or overripe bananas, overripe
avocados
•
•
•
Decongestants
Nasal drops or sprays
Pain relievers* (NB: meperidine is very
dangerous)
•
General and local anesthetics*
•
Stimulants*
•
L-Dopa*
•
Propranolol*
•
Caffeine*
•
•
Soy sauce*
•
•
Raisins*
•
Liver (dangerous when not fresh)
•
* = considered safe in limited amounts
Other antidepressants*
Some herbal preparations, e.g., those
containing ginseng or ma huang
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Selective Serotonin Reuptake
Inhibitors (SSRIs) (1989)
Action of SSRIs
• fluoxetine* (Prozac, Serafem)*, paroxetine (Paxil), sertraline
(Zoloft), fluvoxamine (Luvox), citalopram (Celexa) &
escitalopram (Lexepro) + 2 new
• same effectiveness but more acceptable side effects and
fewer overdose risks
• side effects more like stimulant drugs in most ( 1 in 5 users
might feel anxious, hyper, restless, suffer insomnia, stomach
upset, diarrhea) early in treatment
• too high dose in kids may be mistaken for bipolar disorder;
only fluoxetine shown to be effective in kids
Other Uses for SSRIs
• *Treatment of dysthymia,pre-menstrual dysphoria,
postpartum depression, bipolar depression
• *Used for social phobias, panic disorder, PTSD,
generalized anxiety disorder, OCD
• Treatment of some eating disorders & addictions and
some chronic headaches
SSRI Problems
SSRI-Induced Sexual Dysfunction
Significant proportion (up to 80%) will have sexual side
effects (loss of desire, impotence, difficulty achieving
orgasm)
• Can be serious enough to affect marriages, relationships
Serotonin Syndrome
High Dose or Combining 5HT Drugs Produces an
Exaggerated Response
l Altered cognition (disorientation, confusion, hypomania,
delusions, “losing-it”)
l Behavioral alterations (agitation, restless)
l Autonomic (fever, chills, sweat, diarrhea, hypertension,
tachycardia)
l Neuromuscular impairment (ataxia, hyperreflexia)
l Surprisingly, an SSRI + an opioid analgesic or a benzodiazepine
sometimes triggers serotonin syndrome
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Serotonin Withdrawal Syndrome or “Discontinuation
Syndrome”
• ~ 60% who abruptly stop their SSRI will experience some
of these:
Note “FINISH” mnemonic)
•
•
•
•
•
•
•
Flu-like symptoms (fatigue, aches, chills, diarrhea)
Insomnia or disturbed sleep
Nausea
Imbalance (dizziness, incoordination)
Sensory abnormalities (electric shock sensations, visual)
Hyperarousal (agitation, anxiety) & Headache
Dose should be slowly tapered
Paxil “Termination” Symptoms
• http://www.youtube.com/watch?v=hfQUTHrWnRk&mode=related&s
earch=
• http://www.youtube.com/watch?v=T5X01wvJWPs
• Discontinuation syndrome can also occur after lengthy
use of other antideps
Drugs Not Fitting Above Categories
• Fewer effects on sexual functioning:
• *Wellbutrin (buproprion) (DA/NE reuptake inhibitor somewhat like
cocaine/amphetamine). As a “stimulating” antidep it treats
depression & the fatigue it produces but also has some seizure risk
& can worsen anxiety disorders, OCD, panic.
• Serotonin AND NE reuptake inhibitors– newer “dual action”
• Effexor (venlafaxine) & Pristiq (desvenlafaxine) – fewer sex effects than SSRIs
but not as good as bupropion.
• Watch for “funny stuff” (agitation, aggression, manic flips, homicidality (new
warnings added), not for adolescents
• Cymbalta (duloxetine) (analgesic too)
• Remeron (mirtazapine) (may work somewhat faster; sedative & increases
appetite too)
New Warnings
• Adult and Pediatrics:
• There are clinical trial and post-marketing reports with SSRIs and other newer antidepressants, in both pediatrics and adults, of severe agitation-type adverse events
coupled with self-harm or harm to others. The agitation-type events include:
akathisia, agitation, disinhibition, emotional lability, hostility, aggression,
depersonalization. In some cases, the events occurred within several weeks of
starting treatment.
• Rigorous clinical monitoring for suicidal ideation or other indicators of potential for
suicidal behaviour is advised in patients of all ages. This includes monitoring for
agitation-type emotional and behavioral changes.
• http://www.antidepressantsfacts.com/2004-05-26-HC-suicid-self-harm-effexor.htm (see next
slide)
Beware of Re-Packaged or Slightly Altered Old Drugs to Get a New
Patent & More $$$
• Doxepin  Silenor 50x as expensive
• Celexa Lexepro
• Effexor  Pristiq
Increased Suicidality in Pediatric and Adolescents on
Antidepressants?
• Metanalysis of 24 small studies revealed an increased risk,
particularly when starting the drug or changing dose
• Risk in untreated group: 2/100
• Risk in treated group: 4/100
• So in 2004 FDA require “Black Box” Warnings
* NOTE: New genetic research looks promising for being able to
identify antidep “nonresponders” and also antidep users prone to
suicidal ideation!
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Required “Black Box” Warning
Controversy Has a Cascade Effect
http://www.youtube.com/watch?v=k-BT8nxO8Pg
• But reactionary decrease in antidep use 14-49%
increase in suicides – largest increase since suicide
data began to be collected!!
• http://www.youtube.com/watch?v=bLpuIezmf-w
• Psychotherapy along with meds decreases the
suicide risk.
• http://www.uchospitals.edu/news/2012/20120206
-depression.html
SSRIs and Suicide
Antidepressant Limitations
• Response to antidep may take up to 12 weeks to occur
• Antidepressants only partially effective in many
• Even if first antidep does not work, switching to another may be
successful
• All antideps are effective for some – no single best antidep – need to
match drug with patient
• May be necessary to “augment” treatment – various add-ons:
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•
•
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A second antidepressant (e.g. SSRI+buproprion)
Provigil (modafanil); BuSpar (buspirone)
A mood stabilizer/anticonvulsant like Lamictal (lamotrigine)
An atypical antipsychotic like Abilify (aripiprazole) or Seroquel (quetiapine) or
antipsych/antidep mix (olanzapine+ fluoxetine) Symbyax
• Cognitive-behavioral therapy
New Drug Research
• Several distinctively different antideps are under
investigation.
• One surprising new finding:
• Low dose intravenous ketamine can produce immediate relief
of depressive or serious anxiety symptoms in some
individuals. Typically lasts 1-3 weeks, sometimes longer.
Looking for a non-hallucinogenic drug that might have the
same action.
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